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Enhanced intestinal lymphatic absorption of saquinavir through supersaturated self-microemulsifying drug delivery systems

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Asian Journal of Pharmaceutical Sciences 2020年第3期15卷 336-346页

作者： Kanghee Jo hyeongmin kim Prakash Khadka Taejun Jang Soo Jin kim Seong-Ha Hwang Jaehwi Lee College of Pharmacy Chung-Ang UniversitySeoul 06974Republic of Korea

The therapeutic potential of saquinavir, a specific inhibitor of human immunodeficiency virus(HIV)-1 and HIV-2 protease enzymes, has been largely limited because of a low solubility and consequnt low bioavailability. Thus, we aimed to design a supersaturated selfmicroemulsifying drug delivery system(S-SMEDDS) that can maintain a high concentration of saquinavir in gastro-intestinal fluid thorugh inhibiting the drug precipitation to enhance the lymphatic transport of saquinavir and to increase the bioavailability of saquinavir considerably. Solubilizing capacity of different oils, surfactants, and cosurfactants for saquinavir was evaluated to select optimal ingredients for preparation of *** the construction of pseudo-ternary phase diagram, SMEDDS formulations were established. A polymer as a precipitation inhibitor was selected based on its viscosity and drug precipitation inhibiting capacity. The S-SMEDDS and SMEDDS designed were administered at an equal dose to rats. At predetermined time points, levels of saquinavir in lymph collected from the rats were assessed. SMEDDS prepared presented a proper selfmicroemulsification efficiency and dispersion stability. The S-SMEDDS fabricated using the SMEDDS and hydroxypropyl methyl cellulose 2910 as a precipitation inhibitor exhibited a signficantly enhanced solubilizing capacity for saquinavir. The drug concentration in a simulated intestinal fluid evaluated with the S-SMEDDS was also maintained at higher levels for prolonged time than that examined with the SMEDDS. The S-SMEDDS showed a considerably enhanced lymphatic absoprtion of saquinavir in rats compared to the ***, the S-SMEDDS would be usefully exploited to enhance the lymphatic absorption of hydrophobic drugs that need to be targeted to the lymphatic system.

关键词： Lymphatic drug delivery Self-microemulsifying drug delivery system Saquinavir Precipitation inhibitor Supersaturation Lipid-based formulation

Thin films as an emerging platform for drug delivery

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Asian Journal of Pharmaceutical Sciences 2016年第5期11卷 559-574页

作者： Sandeep Karki hyeongmin kim Seon-Jeong Na Dohyun Shin Kanghee Joa Jaehwi Lee Pharmaceutical Formulation Design Laboratory College of PharmacyChung-Ang UniversitySeoul 06974Republic of Korea Bio-Integration Research Center for Nutra-Pharmaceutical Epigenetics Chung-Ang UniversitySeoul 06974Republic of Korea Center for Metareceptome Research Chung-Ang UniversitySeoul 06974Republic of Korea

Pharmaceutical scientists throughout the world are trying to explore thin films as a novel drug delivery tool. Thin films have been identified as an alternative approach to conventional dosage forms. The thin films are considered to be convenient to swallow, selfadministrable, and fast dissolving dosage form, all of which make it as a versatile platform for drug delivery. This delivery system has been used for both systemic and local action via several routes such as oral, buccal, sublingual, ocular, and transdermal routes. The design of efficient thin films requires a comprehensive knowledge of the pharmacological and pharmaceutical properties of drugs and polymers along with an appropriate selection of manufacturing processes. Therefore, the aim of this review is to provide an overview of the critical factors affecting the formulation of thin films, including the physico-chemical properties of polymers and drugs, anatomical and physiological constraints, as well as the characterization methods and quality specifications to circumvent the difficulties associated with formulation design. It also highlights the recent trends and perspectives to develop thin film products by various companies.

关键词： Thin film Film-forming polymer Mechanical properties Manufacturing Characterization

Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability

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Asian Journal of Pharmaceutical Sciences 2014年第6期9卷 304-316页

作者： Prakash Khadka Jieun Ro hyeongmin kim Iksoo kim Jeong Tae kim Hyunil kim Jae Min Cho Gyiae Yun Jaehwi Lee College of Pharmacy Chung-Ang UniversitySeoul 156-756Republic of Korea Department of Food Science and Technology Chung-Ang UniversityAnseong 456-756Republic of Korea

Pharmaceutical particle technology is employed to improve poor aqueous solubility of drug compounds that limits in vivo bioavailability owing to their low dissolution rate in the gastrointestinal fluids following oral *** particle technology involves several approaches from the conventional size reduction processes to the newer,novel particle technologies that modify the solubility properties of the drugs and produce solid,powdered form of the drugs that are readily soluble in water and can be easily formulated into various dosage *** review highlights the solid particle technologies available for improving solubility,dissolution and bioavailability of drugs with poor aqueous solubility.

关键词： Particle technology Drug solubility Poorly water soluble drug Solubility enhancement Dissolution

Additive manufacturing of flexible 3D surface electrodes for electrostatic adhesion control and smart robotic gripping

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Friction 2023年第11期11卷 1974-1986页

作者： Dong Geun kim hyeongmin JE AJohn HART Sanha kim Department of Mechanical Engineering Korea Advanced Institute of Science and TechnologyDaejeon 34141Republic of Korea Department of Mechanical Engineering Massachusetts Institute of TechnologyCambridgeMA 02139USA

Mechanically flexible surface structures with embedded conductive electrodes are attractive in contact-based devices,such as those used in reversible dry/adhesion and tactile *** shapes of the surface structures strongly determine the contact behavior and therefore the resulting adhesion and sensing functionalities;however,available features are often restricted by fabrication ***,we additively manufacture elastomeric structure arrays with diverse angles,shapes,and sizes;this is followed by integration of conductive nanowire *** fabricated flexible three-dimensional(3D)surface electrodes are mechanically compliant and electrically conductive,providing multifunctional ability to sense touch and to switch adhesion via a combined effect of shear-and electro *** designed soft,anisotropic flexible structures to mimic the gecko’s reversible adhesion,which is governed by van der Waals forces;we integrated nanowires to further manipulate the localized electric field among the adjacent flexible 3D surface electrodes to provide additional means to digitally tune the electrostatic attraction at the contact *** addition,the composite surface can sense the contact force via capacitive *** our flexible 3D surface electrodes,we demonstrate a complete soft gripper that can grasp diverse convex objects,including metal,ceramic,and plastic products,as well as fresh fruits,and that exhibits 72%greater electroadhesive gripping force when voltage is applied.

关键词： electroadhesion tactile sensing robotic gripper additive manufacturing dry adhesive

High-dose hepatitis B immunoglobulin therapy in hepatocellular carcinoma with hepatitis B virus-DNA/hepatitis B e antigen-positive patients after living donor liver transplantation

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World Journal of Gastroenterology 2016年第14期22卷 3803-3812页

作者： Eung Chang Lee Seong Hoon kim Seung Duk Lee hyeongmin Park Soon-Ae Lee Sang-Jae Park Center for Liver Cancer National Cancer Center

AIM: To investigate the impact of high-dose hepatitis B immunoglobulin(HBIG) on hepatocellular carcinoma(HCC) and hepatitis B virus(HBV) recurrence and overall survival after living donor liver transplantation(LDLT).METHODS: We investigated 168 patients who underwent LDLT due to HCC, and who were HBV-DNA/hepatitis B e antigen(HBe Ag)-positive, from January 2008 to December 2013. After assessing whether the patients met the Milan criteria, they were assigned to the low-dose HBIG group and high-dose HBIG group. Using the propensity score 1:1 matching method, 38 and 18 pairs were defined as adhering to and not adhering to the Milan criteria. For each pair, HCC recurrence, HBV recurrence and overall survival were analyzed by the Kaplan-Meier method and the log rank test according to the HBIG dose. RESULTS: Among those who met the Milan criteria, the 6-mo, 1-year, and 3-year HCC recurrence-free survival rates were 88.9%, 83.2%, and 83.2% in the low-dose HBIG group and 97.2%, 97.2%, and 97.2% in the high-dose HBIG group, respectively(P = 0.042).In contrast, among those who did not meet the Milan criteria, HCC recurrence did not differ according to the HBIG dose(P = 0.937). Moreover, HBV recurrence and overall survival did not differ according to the HBIG dose among those who met(P = 0.317 and 0.190, respectively) and did not meet(P = 0.350 and 0.987, respectively) the Milan criteria. CONCLUSION: High-dose HBIG therapy can reduce HCC recurrence in HBV-DNA/HBe Ag-positive patients after LDLT.

关键词： Hepatitis B immune globulin Hepatocellular carcinoma Hepatitis B virus-DNA Liver transplantation Hepatitis B e antigen